Global Prevalence and Incidence Estimates of Oral Lichen Planus: A Systematic Review and Meta-analysis

Changchang Li; Xiaoqiong Tang; Xiaoyan Zheng; Shuqi Ge; Hao Wen; Xiaoqiong Lin; Zhiwei Chen; Liming Lu

doi:10.1001/jamadermatol.2019.3797

. 2020 Jan 2;156(2):172–181. doi: 10.1001/jamadermatol.2019.3797

Global Prevalence and Incidence Estimates of Oral Lichen Planus

A Systematic Review and Meta-analysis

Changchang Li ¹, Xiaoqiong Tang ², Xiaoyan Zheng ³, Shuqi Ge ³, Hao Wen ³, Xiaoqiong Lin ¹, Zhiwei Chen ^1,^✉, Liming Lu ^3,^✉

¹Department of Dermatology, Wenzhou Hospital of Integrated Chinese and Western Medicine, Zhejiang University of Traditional Chinese Medicine, Wenzhou, Zhejiang, China

²Anhui University of Traditional Chinese Medicine, Anhui, China

³Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China

Accepted for Publication: October 13, 2019.

^✉

Corresponding Author: Liming Lu, PhD, Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, 232 Waihuan Dong Rd, Guangzhou 510006, China (lulimingleon@126.com); Zhiwei Chen, MD, Department of Dermatology, Wenzhou Hospital of Integrated Chinese and Western Medicine, Zhejiang University of Traditional Chinese Medicine, 75 Jin Xiu Rd, Wenzhou, Zhejiang 325000, China (wz75czw@163.com).

Published Online: January 2, 2020. doi:10.1001/jamadermatol.2019.3797

Author Contributions: Drs Chen and Lu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Li and Tang contributed equally to this work.

Concept and design: Li, Tang, Chen, Lu.

Acquisition, analysis, or interpretation of data: Li, Tang, Zheng, Wen, Ge, Lin, Lu.

Drafting of the manuscript: Li, Tang, Zheng, Wen.

Critical revision of the manuscript for important intellectual content: Li, Tang, Zheng, Ge, Lin, Chen, Lu.

Statistical analysis: Li, Tang, Zheng, Wen, Lu.

Obtained funding: Zheng, Lu.

Administrative, technical, or material support: Lu.

Supervision: Wen, Chen, Lu.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was funded by the First-Class Discipline Construction Foundation of Guangzhou University of Chinese Medicine (Chinese Medicine Department), the Young Top Talent Project of Scientific and Technological Innovation in Special Support Plan for Training High-level Talents in Guangdong (grant 2017TQ04R627), and the Youth Research and Cultivation Project of Guangzhou University of Chinese Medicine (grant A1-AFD018191A40).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

^✉

Corresponding author.

PMCID: PMC6990670 PMID: 31895418

This systematic review and meta-analysis identifies the global prevalence and incidence of oral lichen planus in the overall population and among subgroups.

Key Points

Question

What are the global prevalence and incidence of oral lichen planus?

Findings

In this systematic review and meta-analysis of 46 studies, 15 included general population data (n = 462 993), and 31 included information from clinical patients (n = 191 963). The overall estimated pooled prevalence of oral lichen planus was 0.89% among the general population and 0.98% among clinical patients.

Meaning

This study identified the global prevalence and incidence of oral lichen planus in terms of its spatial, temporal, and population distribution.

Abstract

Importance

Integrated information on the global prevalence and incidence of oral lichen planus (OLP) is lacking.

Objective

To examine the global prevalence and incidence of OLP in a systematic review and meta-analysis.

Data Sources

A systematic review of population-based studies and clinic-based studies reporting the prevalence and incidence of OLP was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. The search terms included “(lichen planus or LP) and (prevalence or incidence or epidemiology).” No language restriction was applied.

Study Selection

Observational descriptive studies investigating the prevalence and incidence of OLP were included.

Data Extraction and Synthesis

Data were extracted by continent, sex, and other characteristics. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.

Main Outcomes and Measures

The primary outcome was the prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using the I² statistic.

Results

Among 46 studies, the overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%) among the general population (n = 462 993) and 0.98% (95% CI, 0.67%-1.43%) among clinical patients (n = 191 963). Among the 15 population-based studies, the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia, 1.68% (95% CI, 1.09%-2.58%) in Europe, and 1.39% (95% CI, 0.58%-3.28%) in South America. Among the 31 clinic-based studies, the prevalence was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia, 1.03% (95% CI, 0.51%-2.09%) in Europe, 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America. The pooled prevalence of OLP by sex was 1.55% (95% CI, 0.83%-2.89%) for women and 1.11% (95% CI, 0.57%-2.14%) for men in the population-based studies and 1.69% (95% CI, 1.05%-2.70%) for women and 1.09% (95% CI, 0.67%-1.77%) for men in the clinic-based studies. In 5 clinic-based studies providing the age distribution of patients with OLP, the prevalence by age was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older.

Conclusions and Relevance

This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. The overall estimated pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. The findings should be considered with caution because of the high heterogeneity of the included studies.

Introduction

Oral lichen planus (OLP) is a T-cell–mediated and chronic inflammatory disorder affecting the oral mucosa,1 with an incidence that is higher in women than in men. The affected age range varies around the world,² and the disease is rare in children.³ Smokers and patients who abuse alcohol have a higher prevalence of OLP.⁴

Oral lichen planus can be caused or triggered by a genetic malfunction or by environmental factors. Although the cause remains unknown, the immunological system plays a substantial role, and several factors are well known, such as psychological stress, drug intake, and anxiety.^5,6,7 Oral lichen planus may be associated with some systemic diseases, including hepatitis C virus infection, hypertension, diabetes, graft-vs-host disease, and thyroid dysfunction.^8,9,10,11 However, the precise role of most of these conditions in OLP remains unclear.

It is a challenge to diagnose OLP, particularly in the absence of the classic reticular pattern on oral mucosal surfaces.¹² Therefore, an oral biopsy with histopathological examination is usually required to confirm the clinical diagnosis and exclude dysplasia and cancer.¹³ Furthermore, oral lichenoid lesions, such as lichenoid contact lesions, lichenoid drug reactions, and lichenoid lesions of graft-vs-host disease, may confuse the differential diagnosis. In 1978, the World Health Organization published a set of clinicopathological criteria to better define the criteria for diagnosis of OLP.¹⁴ However, these criteria lacked consensus regarding clinical and histological diagnosis of OLP. In 2003, modifications were proposed to the World Health Organization criteria,¹⁵ which identified an association between oral lichenoid lesions and OLP. Direct immunofluorescence, although not specific for OLP, is a key tool in differentiating some lichenoid lesions, including erythematous lupus, chronic ulcerative stomatitis, and lichen planus pemphigoid, especially when they have overlapping clinicopathological features.^1,16 Therefore, combinations of clinical findings, histopathological examination results, and direct immunofluorescence can help achieve an accurate diagnosis.

Integrated information about the global prevalence and incidence of OLP is lacking. Therefore, we performed a systematic review and meta-analysis of the published literature (1) to examine the global prevalence and incidence of OLP both among the general population and among clinical patients and (2) to analyze the association between prevalence and possible related variables (eg, publication year, geographic location, sex and age distribution, and diagnostic methods).

Methods

Literature Search

In this systematic review and meta-analysis, a literature search was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. Searches were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search terms included “(lichen planus or LP) and (prevalence or incidence or epidemiology)” (the search strategy is provided in eAppendix 1 in the Supplement). No language restriction was applied. The final search was conducted on March 10, 2019.

Inclusion and Exclusion Criteria

We predefined the inclusion criteria for eligible studies as follows: (1) original investigations; (2) observational studies with a cross-sectional, case-control, or cohort design; and (3) reports of the point prevalence of OLP or sufficient data to calculate OLP among the general population or among clinical patients. There were no restrictions regarding publication year. If more than 1 study evaluated the same population, only the larger study was included. Studies were excluded if (1) they were review articles, case reports, protocols, short communications, personal opinions, letters, posters, conference abstracts, or laboratory research; (2) they did not report sufficient data, and efforts to contact the authors were unsuccessful; or (3) they did not involve patients with OLP.

Data Extraction

The articles were screened for relevance in the title and abstract. The relevant abstracts and any articles without abstracts were selected for full-text review. Two of us (C.L. and X.T.) collected information from the included studies independently and cross-checked the information to ensure the integrity of the contents. Discrepancies were resolved by discussion with a third one of us (X.Z.). We inserted the data into 2 tables, with one listing the population-based studies (Table 1 and eTable 1 in the Supplement) and the other listing the clinic-based studies (Table 2 and eTable 2 in the Supplement). The gathered data included author, publication year, country, continent, sex and age, study period, diagnosis, interviewer, quality appraisal score, sample size, and estimated prevalence.

Table 1. Characteristics of 15 Population-Based Studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} of Oral Lichen Planus (OLP).

Source	Continent	No.		Prevalence, %	Age, y	Study Period	Diagnostic Method
Source	Continent	OLP	Total	Prevalence, %	Age, y	Study Period	Diagnostic Method
Chher et al,¹⁷ 2018 (Cambodia)	Asia	28	1634	1.71	≥18	NR	C
Mehrotra et al,¹⁸ 2017 (India)	Asia	81	402 669	0.02	≥15	NR	C
Feng et al,¹⁹ 2015 (China)	Asia	90 Male: 38 Female: 52	11 054 Male: 5140 Female: 5914	0.81	All ages	2012-2013	C
Carrard et al,²⁰ 2011 (Brazil)	South America	14 Male: 9 Female: 5	1586 Male: 719 Female: 867	0.88	14-104	2001	C(P)
Chung et al,²¹ 2005 (China)	Asia	32 Male: 19 Female: 13	1075 Male: 526 Female: 549	2.98	≥15	1998-1999	C
Espinoza et al,²³ 2003 (Chile)	South America	19 Male: 2 Female: 17	889 Male: 338 Female: 551	2.14	≥65	NR	C
Jahanbani,²² 2003 (Iran)	Asia	6	1167 Male: 1070 Female: 97	0.51	18-69	NR	C + P
García-Pola Vallejo et al,²⁴ 2002 (Spain)	Europe	10 Male: 4 Female: 6	308 Male: 138 Female: 170	3.25	≥30	1997-1998	C
Reichart,²⁵ 2000 (Germany)	Europe	21	2022	1.04	35-44 For younger adults 65-74 For senior citizens	NR	C
Kovač-Kavčič and Skalerič,²⁶ 2000 (Slovenia)	Europe	13 Male: 4 Female: 9	555 Male: 263 Female: 292	2.34	25-75	1983-1987	C
Zain et al,²⁷ 1997 (Malaysia)	Asia	45 Male: 21 Female: 24	11 697 Male: 4698 Female: 6999	0.38	≥25	5 mo	C
Ikeda et al,²⁸ 1995 (Cambodia)	Asia	24 Female: 24	1319 Male: 366 Female: 953	1.82	15-99	1991	C
Vigild,²⁹ 1987 (Denmark)	Europe	3	685	0.44	≥60	NR	C
Axéll and Rundquist,³⁰ 1987 (Sweden)	Europe	410 Male: 154 Female: 256	20 333	2.02	≥15	NR	C(P)
Lay et al,³¹ 1982 (Burma)	Asia	23	6000	0.38	≥15	NR	C

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Abbreviations: C, clinical diagnosis; C(P), after clinical diagnosis, histopathological diagnostic procedures were performed if necessary; C + P, both clinical diagnosis and pathological diagnosis; NR, not reported.

Table 2. Characteristics of 31 Clinic-Based Studies^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} of Oral Lichen Planus (OLP).

Source	Continent	No.		Prevalence, %	Study Period	Diagnostic Method
Source	Continent	OLP	Total	Prevalence, %	Study Period	Diagnostic Method
Kansky et al,³² 2018 (Slovenia)	Europe	26	2395 Male: 904 Female: 1491	1.09	Spring 2017	C
Al-Maweri et al,³³ 2018 (Yemen)	Asia	25 Male: 9 Female: 16	1052 Male: 588 Female: 464	2.38	2015	C(P)
Tortorici et al,³⁴ 2016 (Italy)	Europe	37 Male: 15 Female: 22	2539 Male: 1209 Female: 1330	1.46	2012-2015	C + P
Varghese et al,³⁵ 2016 (India)	Asia	122 Male: 43 Female: 79	29 606	0.41	2014-2015	C + P
Mostafa and Ahmed,³⁶ 2015 (Egypt)	Africa	64 Male: 20 Female: 44	4470 Male: 1397 Female: 3073	1.43	2012-2014	C(P)
Gupta et al,³⁷ 2014 (India)	Asia	15	471	3.18	2006-2009	C + P
Hegde et al,⁶² 2014 (India)	Asia	24 Male: 20 Female: 4	2000 Male: 1132 Female: 868	1.20	2012	C
Al-Maweri and Al-Sufyani,³⁸ 2013 (Yemen)	Asia	2 Male: 1 Female: 1	304 Male: 206 Female: 98	0.66	NR	C
Hassona et al,³⁹ 2014 (Jordan)	Asia	9	1041	0.86	2013-2014	C + P
Babu et al,⁴⁰ 2014 (India)	Asia	12 Male: 4 Female: 8	3500 Male: 1597 Female: 1903	0.34	2012	C(P)
do Carmo et al,⁴¹ 2014 (Brazil)	South America	250	25 435	0.98	1957-2012	C + P
Bhatnagar et al,⁴² 2013 (India)	Asia	71 Male: 39 Female: 32	8866 Male: 5187 Female: 3679	0.80	2010	C
Brzak et al,⁴³ 2012 (Croatia)	Europe	537	12 508	4.29	1998-2007	C + P
Omal et al,⁴⁴ 2012 (India)	Asia	82	18 306	0.45	2008-2010	C + P
Mehrotra et al,⁴⁵ 2010 (India)	Asia	6	3030	0.20	2008	C(P)
Oliveira Alves et al,⁴⁶ 2010 (Brazil)	South America	110	1822	6.04	1989-2009	C(P)
Al-Mobeeriek and AlDosari,⁴⁷ 2009 (Saudi Arabia)	Asia	9	2552	0.35	2002-2005	C
Cebeci et al,⁴⁸ 2009 (Turkey)	Asia	58	5018	1.16	2004-2005	C + P
Mathew et al,⁴⁹ 2008 (India)	Asia	15 Male: 9 Female: 6	1190 Male: 747 Female: 443	1.26	2005	C(P)
Pentenero et al,⁵⁰ 2008 (Italy)	Europe	60 Male: 26 Female: 34	4098 Male: 2040 Female: 2058	1.46	1996-2003	C(P)
Delilbaşi et al,⁵¹ 2003 (Turkey)	Asia	22 Male: 8 Female: 14	2000 Male: 927 Female: 1073	1.10	1998-2001	C(P)
Jainkittivong et al,⁵² 2002 (Thailand)	Asia	14 Male: 1 Female: 13	500 Male: 194 Female: 306	2.80	NR	C
Bokor-Bratić and Picuric,⁵³ 2001 (Yugoslavia)	Europe	39 Male: 10 Female: 29	2385 Male: 1288 Female: 1097	1.64	1988-1990	C(P)
Femopase et al,⁵⁴ 1997 (Argentina)	South America	476 Male: 166 Female: 310	9021 Male: 3602 Female: 5419	5.28	1988-1992	C(P)
Reichart and Kohn,⁵⁵ 1996 (Germany)	Europe	6 Male: 3 Female: 3	1000 Male: 506 Female: 494	0.60	1991-1992	C(P)
Bánóczy and Rigó,⁵⁶ 1991 (Hungary)	Europe	6	7820 Male: 3358 Female: 4462	0.08	1987-1988	C(P)
Axéll et al,⁵⁷ 1990 (Thailand, Malaysia)	Asia	14 Male: 3 Female: 11	467 Male: 241 Female: 226	3.00	NR	C(P)
Salem,⁵⁸ 1989 (Saudi Arabia)	Asia	72 Male: 40 Female: 32	4277 Male: 2695 Female: 1582	1.68	1982-1987	C + P
Bouquot and Gorlin,⁵⁹ 1986 (United States)	North America	26	23 616	0.11	1957-1973	C(P)
Mani,⁶⁰ 1985 (Saudi Arabia)	Asia	4	674	0.59	1983	C
Pindborg et al,⁶¹ 1965 (India)	Asia	19	10 000	0.19	121 d	C

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Quality Assessment

The risk of bias of the included studies was independently assessed using the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data⁶³ by 2 of us (C.L. and X.T.). Another one of us (S.G.) was involved in the event of ambiguity (eTable 1 in the Supplement). There were 9 items in total: (1) Was the sample frame appropriate to address the target population? (2) Were study participants sampled in an appropriate way? (3) Was the sample size adequate? (4) Were the study participants and the setting described in detail? (5) Was the data analysis conducted with sufficient coverage of the identified sample? (6) Were valid methods used for identification of the condition? (7) Was the condition measured in a standard, reliable way for all of the participants? (8) Was there an appropriate statistical analysis? (9) Was the response rate adequate? If not, was the low response rate managed appropriately? Higher total scores indicated better quality and lower risk of a study. Studies were categorized based on the percentage of yes answers as high quality (≤49%), moderate quality (50%-69%), or low quality (≥70%).

Data Analysis

Data analysis was performed using the metaprop module in the R statistical software package, version 3.5.3. We previously adopted the logit method to transform the prevalence reported in each study, followed by an inverse-variance–weighted random-effects meta-analysis using the method by DerSimonian and Laird.⁶⁴ Next, we obtained the pooled prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using the I² statistic and the P value for heterogeneity (Cochrane Q statistic), which describe the percentage of variation across studies that is due to heterogeneity rather than pure chance. Forest plots were used to show the results graphically. Publication bias was assessed using the Egger test and was shown using funnel plots. The amount of true heterogeneity (the variance or the SD) was indicated by τ². We also considered 2 different estimators of residual heterogeneity (I² and τ²) in random-effects meta-regression using metafor in the R package.⁶⁵ To test whether subgroup associations were credible or not, we developed 2 hypotheses (subgroup by continent and subgroup by diagnostic methods) to explain variability in effect estimates of the primary outcome, which was the prevalence of OLP among the overall population and among subgroups. Subgroup analysis was performed based on continent, sex and age, and diagnostic methods. The following 3 diagnostic methods are described in the present study: C, indicating clinical diagnosis; P, indicating pathological diagnosis; and C(P), indicating that after clinical diagnosis histopathological diagnostic procedures were performed if necessary. Two-sided P < .05 was considered statistically significant.

Results

Literature Search and Included Studies

Using the search term “(lichen planus or LP) and (prevalence or incidence or epidemiology)” resulted in 7804 records from the 3 databases. The PRISMA flow diagram shows the search history (Figure 1). This search resulted in the inclusion of 46 studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} (full citation details of the included studies are provided in eAppendix 2 in the Supplement), 15 of which were population-based studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} (n = 462 993) and 31 of which were clinic-based studies^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} (n = 191 963), with sample sizes ranging from 304 to 402 669.

Figure 1. — OLP indicates oral lichen planus; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

The 15 population-based studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} represented 13 different countries (Table 1). Two studies^20,23 were conducted in South America, 5 studies^{24,25,26,29,30} in Europe, and 8 studies^{17,18,19,21,22,27,28,31} in Asia. Among these 15 studies, 2 reported the prevalence of OLP in Cambodia,^17,28 and 2 reported the prevalence of OLP in China.^19,21

The 31 clinic-based studies^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} represented 17 different countries (Table 2). Seven studies^{32,34,43,50,53,55,56} were conducted in Europe, 19 in Asia,^{33,35,37,38,39,40,42,44,45,47,48,49,51,52,57,58,60,61,62} 3 in South America,^41,46,54 1 in Africa,³⁶ and 1 in North America.⁵⁹ Among these 31 studies, 9 reported the prevalence of OLP in India,^{35,37,40,42,44,45,49,61,62} 3 in Saudi Arabia,^47,58,60 2 in Yemen,^33,38 2 in Italy,^34,50 2 in Brazil,^41,46 2 in Turkey,^48,51 and 2 in Thailand.^52,57

Incidence of OLP

Only 3 studies reported on the incidence of OLP. For a study⁶⁶ in South India, the incidence was 2.48 (95% CI, 2.12-2.83) per 1000 person-years, with rates of 2.14 (95% CI, 1.65-2.64) per 1000 person-years for men and 2.76 (95% CI, 2.25-3.27) per 1000 person-years for women. Based on a 10-year follow-up period, the highest incidence was in the group aged 55 to 64 years for men and in the group aged 45 to 54 years for women. However, a study⁶⁷ in Japan reported that the age-adjusted incidence of OLP was 59.7 (95% CI, 7.4-112.1) per 100 000 person-years for men and 188.0 (95% CI, 96.0-280.1) per 100 000 person-years for women, rates that were somewhat lower than those reported from South India. A recent study⁶⁸ in the United States showed that the incidence of OLP was 11.4 (95% CI, 10.1-12.7) per 100 000 person-years, with rates of 8.1 (95% CI, 6.5-9.6) per 100 000 person-years for men and 14.4 (95% CI, 12.3-16.4) per 100 000 person-years for women.

Overall Prevalence of OLP

Prevalence estimates for OLP derived by meta-analysis are shown in Figure 2 and Figure 3. Estimates for the population-based studies ranged from 0.02% to 3.25% (Figure 2), and the random-effects overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%), with very high heterogeneity (I² = 99%; P < .001). Estimates for the clinic-based studies (most patients visited the stomatology clinic) ranged from 0.08% to 6.04% (Figure 3), and the random-effects pooled overall estimated prevalence of OLP was 0.98% (95% CI, 0.67%-1.43%) (I² = 99%; P < .001).

Prevalence of OLP by Diagnostic Methods

When the studies were categorized by different diagnostic methods of OLP, similar pooled proportions of OLP were found among different subgroups (eFigure 1 and eFigure 2 in the Supplement). Twelve^{17,18,19,21,23,24,25,26,27,28,29,31} of the 15 population-based studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} diagnosing OLP were based on clinic visits (n = 439 907), and the combined prevalence estimate of OLP was 0.86% (95% CI, 0.30%-2.47%), with very high heterogeneity (I² = 99%; P < .01). Only 1 study²² was based on both clinical diagnosis and pathological diagnosis (n = 1167), and the prevalence estimate of OLP was 0.51% (95% CI, 0.23%-1.14%).

Two studies^20,30 were based on histopathological diagnostic procedures after clinical diagnosis (n = 21 919). The prevalence estimate of OLP was 1.39% (95% CI, 0.62%-3.09%). The prevalence estimate of OLP was 1.39% (95% CI, 0.62%-3.09%), with very high heterogeneity (I² = 89%; P < .01).

Among the 31 clinic-based studies,^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} 8 studies^{32,38,42,47,52,60,61,62} reported the prevalence of OLP by clinical diagnosis (n = 27 291), with a combined prevalence estimate of OLP of 0.74% (95% CI, 0.43%-1.28%), and the random-effects overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%), with very high heterogeneity (I² = 91%; P < .01). Nine studies^{34,35,37,39,41,43,44,48,58}diagnosed OLP based on both clinical diagnosis and pathological diagnosis (n = 99 201), and the combined prevalence estimate of OLP was 1.23% (95% CI, 0.61%-2.44%), with very high heterogeneity (I² = 99%; P < .01). The remaining 14 studies^{33,36,40,45,46,49,50,51,53,54,55,56,57,59} with histopathological diagnostic procedures after clinical diagnosis (n = 65 471) showed that the prevalence estimate of OLP was 0.97% (95% CI, 0.52%-1.81%), with very high heterogeneity (I² = 98%; P < .01).

Only 1 study⁴⁰ diagnosed OLP with combined clinicopathological and direct immunofluorescence methods when there was suspicion of other diseases (n = 3500). The prevalence estimate of OLP was 0.34%.

Prevalence of OLP by Publication Year

To understand whether there was an association between time and the prevalence of OLP, we ran an association analysis on publication year (eFigure 3 in the Supplement). The graph shows that the prevalence of OLP fluctuated with publication year, ranging from 0.02% in 1965 to 3.25% in 2002 among the population-based studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} and ranging from 0.08% in 1991 to 6.04% in 2010 among the clinic-based studies.^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} According to the scatterplot, no statistically significant association was observed between a higher or lower prevalence of OLP and publication year.

Prevalence of OLP by Continent

Most of the 15 population-based studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} were from Asia (n = 436 615), only 5 were from Europe (n = 23 903),^{24,25,26,29,30} and 2 were from South America (n = 2475).^20,23 The 31 clinic-based studies^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} were more widespread across the world, with 19 from Asia (n = 94 854),^{33,35,37,38,39,40,42,44,45,47,48,49,51,52,57,58,60,61,62} 7 from Europe (n = 32 745),^{32,34,43,50,53,55,56} 3 from South America (n = 36 278),^41,46,54 1 from Africa (n = 4470),³⁶ and 1 from North America (n = 23 616).⁵⁹ Among the 15 population-based studies,^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia (with very high heterogeneity [I² = 99%; P < .01]), 1.68% (95% CI, 1.09%-2.58%) in Europe (with very high heterogeneity [I² = 79%; P < .01]), and 1.39% (95% CI, 0.58%-3.28%) in South America (with very high heterogeneity [I² = 84%; P = .01]) (eFigure 4 in the Supplement). Among the 31 clinic-based studies,^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} the prevalence of OLP was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia (with very high heterogeneity [I² = 94%; P < .01]), 1.03% (95% CI, 0.51%-2.09%) in Europe (with very high heterogeneity [I² = 99%; P < .01]), 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America (with very high heterogeneity [I² = 100%; P < .01]) (eFigure 5 in the Supplement).

Prevalence of OLP by Sex

A sex difference in the prevalence of OLP was observed between the 15 population-based studies^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} and the 31 clinic-based studies.^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} Among the 15 population-based studies,^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} only 8 studies^{19,20,21,23,24,26,27,28} reported the number of men and women with and without OLP, and 1 study²⁸ included only women. These 9 studies included a total of 16 295 women (57.2%) and 12 188 men (42.8%). The pooled prevalence of OLP was 1.55% (95% CI, 0.83%-2.89%) for women (with very high heterogeneity [I² = 93%; P < .01]) and 1.11% (95% CI, 0.57%-2.14%) for men (with very high heterogeneity [I² = 88%; P < .01]) (eFigure 6 in the Supplement). Among the 31 clinic-based studies,^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} 15 studies^{33,34,36,38,40,42,49,51,52,53,54,55,57,58,62} reported the prevalence of OLP by sex, with 22 055 women (50.6%) and 21 516 men (49.4%). The pooled proportions of OLP were 1.69% (95% CI, 1.05%-2.70%) for women (with very high heterogeneity [I² = 95%; P < .01]) and 1.09% (95% CI, 0.67%-1.77%) for men (with very high heterogeneity [I² = 93%; P < .01]) (eFigure 7 in the Supplement). The prevalence of OLP appeared to be lower among men than among women.

Prevalence of OLP by Age

Most of the 46 studies included individuals older than 15 years. Two population-based studies^23,29 and 1 clinic-based study⁵² examined geriatric patients 60 to 65 years and older, whereas 4 clinic-based studies^37,43,57,61 did not report any data on age. Only 5 clinic-based studies^{33,44,49,50,53} provided the age distribution of patients with OLP. The results of these 5 studies indicated that the prevalence of OLP was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years (with very high heterogeneity [I² = 78%; P < .01]) and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older (with very high heterogeneity [I² = 89%; P < .01]) (eFigure 8 in the Supplement).

Publication Bias

Among the 15 population-based studies,^{17,18,19,20,21,22,23,24,25,26,27,28,29,30,31} Egger test indicated that there was no statistically significant publication bias (P > .05). However, among the 31 clinic-based studies,^{32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62} Egger test showed statistically significant publication bias (P < .05) (eAppendix 3 in the Supplement). Therefore, publication bias could be a source of heterogeneity.

Metaregression

Metaregression showed that neither continent nor diagnostic methods could be a source of heterogeneity (P > .05) (eTable 2 in the Supplement). Heterogeneity between the included studies was also accounted for (I² = 0% and τ² = 0).

Discussion

To the best of our knowledge, this is the first systematic review and meta-analysis of the global prevalence and incidence estimates of OLP among both the general population and clinical patients. This analysis showed that the overall estimated prevalence of OLP is 0.89% among the general population and 0.98% among clinical patients. The present study also provided evidence that the prevalence of OLP is higher among women compared with men, predominantly affecting those aged 40 years and older. Moreover, the prevalence of OLP is lower in Asian countries than in non-Asian countries. No publication year–dependent gradient in the prevalence of OLP was observed. Our findings should be considered with caution because of the high heterogeneity of the included studies.

There was high heterogeneity among the studies addressing the prevalence and incidence of OLP for several possible reasons. Because of the insufficient understanding of diagnostic criteria for the clinical diagnosis of OLP resulting from the variety of clinical and pathological features that may be present, it was challenging for the OLP diagnosis to inevitably depend on physician experience, especially when clinical manifestations are atypical. Moreover, it is difficult to distinguish OLP from other oral mucosal disease, such as chronic ulcerative stomatitis and lichen planus pemphigoid, which may exhibit some lichenoid features clinically or histologically. In this context, direct immunofluorescence is of great value. Therefore, the lack of precise diagnosis in studies likely altered the reported prevalence of OLP. A more fundamental concern is that study participants were typically examined only once; therefore, the prevalence of OLP may be underestimated because of the fluctuating nature of the disease. In many patients, the onset of OLP was insidious, and they may have been unaware of their oral condition. Those with mild or moderate OLP might not have sought medical treatment, especially for the nonerosive type of OLP, which manifests no discomfort in approximately one-third of individuals, or they may have only roughness of the lining of the mouth, resulting in false low prevalence estimates in studies.^13,69 In addition, methodological heterogeneity is important to consider. Prevalence and incidence data may be derived from various study designs with differing levels of methodological quality, such as different study populations, sampling methods, coverage of the identified sample, sample sizes, data collection, participant cooperation, and professional level of the examiner, resulting in differences among the studies.

Subgroup analysis by continent confirmed a lower prevalence of OLP in Asian countries than in non-Asian countries. The highest prevalence (6.04%) was reported for a sample in Brazil,⁴⁶ whereas the lowest prevalence (0.02%) was reported for a sample in India.¹⁸ A possible explanation for this variation might be socioeconomic and sociocultural differences between the populations. Another potential reason may be differences in the screening methods used as well as variations in the prevalence of OLP among the general population of the respective countries. Regional variation, seasonal and climate differences, lifestyle habits (eg, smoking and drinking), eating habits (eg, a spicy diet or the manner of chewing), and life stresses have important roles in the prevalence of OLP. Smokers and patients who abuse alcohol have a higher prevalence of OLP.⁴ This factor may explain why the highest prevalence of OLP (6.04%) was found in Brazil, where 18.18% of residents report being smokers and 29.09% report consumption of alcoholic beverages.⁴⁶

Subgroup analysis by sex showed that the prevalence of OLP was higher among women than among men. Possible reasons are that female hormone levels, such as estrogen and progesterone, tend to fluctuate, especially during menstruation or menopause, and that different social roles may lead to the body being in a state of stress. One study⁷⁰ demonstrated that the incidence of OLP is higher in perimenopausal women than in the general population and increases statistically significantly with greater severity of depression. Oral lichen planus in perimenopausal women can be mediated by declining levels of estrogen and progesterone that directly or indirectly may cause depression, which can trigger OLP. An additional explanation may be that OLP is a T-cell–mediated immunological disease. Another study⁷¹ demonstrated that women are more susceptible to some immune-mediated inflammatory diseases than men (eg, systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis).

Subgroup analysis by age indicated that the prevalence of OLP was higher among patients 40 years and older than among patients younger than 40 years. This difference could be attributed to long-standing oral habits. In addition, the oral mucosa undergoes age-related changes (eg, thinning of mucosa, decreased elasticity, less saliva secretion, and greater tissue permeability),⁷² increasing the risk of OLP. Furthermore, older individuals may not pay as much attention to their oral health. Finally, OLP may also be associated with metabolic changes during aging or with decreased immunity, nutritional deficiencies, medication use, or denture wear.

The high statistical heterogeneity in our study suggests that differences in prevalence estimates between the studies cannot be explained by random chance alone. Rather, the differences in prevalence estimates may be altered by factors like publication bias, difficulty in diagnosing OLP, different demographic characteristics, and regional disparity among the studies.

Limitations

There are several limitations of our systematic review and meta-analysis. First, random error is always a concern, although our analysis was based on a total of 654 956 individuals. We did not have access to some databases (eg, the grey literature), which may have allowed us to obtain additional epidemiological information. Second, few studies have reported a detailed age stratification. Third, early studies^31,60,61 in particular had 1 or more of the following defects with respect to the accuracy of diagnoses: lack of accepted clinical criteria, absence of or no criteria for histological verification, missing immunofluorescence examination, or omitted differential diagnosis.

Conclusions

This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. We estimated that the overall pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. Our findings should be considered with caution because of the high heterogeneity of the included studies.

Supplement.

eAppendix 1. Search Strategy

eTable 1. Quality Assessment

eAppendix 2. Full Citation Details of Included Studies

eFigure 1. Forest Plot of the Prevalence of OLP by Diagnostic Method in Population-Based Studies

eFigure 2. Forest Plot of the Prevalence of OLP by Diagnostic Method in Clinic-Based Studies

eFigure 3. Association Between Prevalence of OLP and Publication Year

eFigure 4. Forest Plot of the Prevalence of OLP by Continent in Population-Based Studies

eFigure 5. Forest Plot of the Prevalence of OLP by Continent in Clinic-Based Studies

eFigure 6. Forest Plot of the Prevalence of OLP by Sex in Population-Based Studies

eFigure 7. Forest Plot of the Prevalence of OLP by Sex in Clinic-Based Studies

eFigure 8. Forest Plot of the Prevalence of OLP by Age in Clinic-Based Studies

eAppendix 3. Publication Bias

eTable 2. Meta-regression of the Prevalence of OLP

eReferences.

Click here for additional data file.^{(502.8KB, pdf)}

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